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2017 ; 11
(3
): e0005348
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
AZALEP a randomized controlled trial of azathioprine to treat leprosy nerve
damage and Type 1 reactions in India: Main findings
#MMPMID28358815
Lockwood DN
; Darlong J
; Govindharaj P
; Kurian R
; Sundarrao P
; John AS
PLoS Negl Trop Dis
2017[Mar]; 11
(3
): e0005348
PMID28358815
show ga
BACKGROUND: Leprosy Type 1 reactions are difficult to treat and only 70% of
patients respond to steroid treatment. Azathioprine has been used as an
immune-suppressant and we tested its efficacy in treating leprosy T1R.
METHODOLOGY: Randomised controlled trial adding azathioprine to steroid treatment
for leprosy reactions. This trial was conducted in four leprosy hospitals in
India. Patients with a new leprosy Type 1 reaction affecting either skin or nerve
were recruited. They were given a 20 week course of oral prednisolone either with
placebo or azathioprine 50mg for 24, 36 or 48 weeks. Outcomes were measured using
a verified combined clinical reaction severity score (CCS) and the score
difference between baseline and end of study calculated. An intention to treat
analysis was done on the 279 patients who had an outcome. PRINCIPAL FINDINGS: 345
patients were recruited, 145 were lost due to adverse events, loss to follow up
or death. 36% needed extra steroids due to a recurrence of their skin and/or
nerve reaction. 76% of patients had improvements in their CCS the end of the
study, 22% had no change and 1.1% deteriorated. Adding azathioprine to steroid
treatment did not improve CCS. So the improvements were attributable to treatment
with steroids. We analysed the skin, sensory and motor scores separately and
found that skin improvement contributed most with 78.9% of patients having skin
improvement, azathioprine treatment for 48 weeks improved sensory scores it also
improved motor scores but so did treatment with prednisolone alone. We identified
significant adverse effects attributable to steroid treatment. When azathioprine
and Dapsone were given together significant numbers of patients developed
significant anaemia. CONCLUSIONS: Azathioprine is not recommended for the
treatment of leprosy reactions and does not improve steroid treatment. Recurrent
reactions are a major challenge. We have also identified that 65% of patients
with sensory and 50% with motor nerve damage do not improve. Future studies
should test giving azathioprine in the treatment of nerve damage and giving a
higher dose for 48 weeks to patients. These findings highlight the difficulty in
switching off leprosy inflammation and the need for better treatments for
reactions and nerve damage. There is also a research need to identify patients
who have recurrences and optimize treatments for them. Patients with recurrences
may benefit from combined treatment with steroids and azathioprine. We have also
shown that significant numbers of patients treated with steroids develop adverse
effects and this needs to be highlighted in leprosy programmes. Research is
needed to identify patients who do not respond to steroid treatment and develop
alternative treatments for them. TRIAL REGISTRATION: ClinicalTrials.gov This
trial was registered with the Indian Council of Medical research clinical Trial
register as a clinical trial Number-REFCTRI/2016/12/007558.